How do species barriers decay? Concordance and local introgression in mosaic hybrid zones of mussels.

The Mytilus complex of marine mussel species forms a mosaic of hybrid zones, found across temperate regions of the globe. This allows us to study 'replicated' instances of secondary contact between closely related species. Previous work on this complex has shown that local introgression is both widespread and highly heterogeneous, and has identified SNPs that are outliers of differentiation between lineages. Here, we developed an ancestry-informative panel of such SNPs. We then compared their frequencies in newly sampled populations, including samples from within the hybrid zones, and parental populations at different distances from the contact. Results show that close to the hybrid zones, some outlier loci are near to fixation for the heterospecific allele, suggesting enhanced local introgression, or the local sweep of a shared ancestral allele. Conversely, genomic cline analyses, treating local parental populations as the reference, reveal a globally high concordance among loci, albeit with a few signals of asymmetric introgression. Enhanced local introgression at specific loci is consistent with the early transfer of adaptive variants after contact, possibly including asymmetric bi-stable variants (Dobzhansky-Muller incompatibilities), or haplotypes loaded with fewer deleterious mutations. Having escaped one barrier, however, these variants can be trapped or delayed at the next barrier, confining the introgression locally. These results shed light on the decay of species barriers during phases of contact.ANR, France; Russian Science Foundatio

To the very End. A contrastive study of N-Rhemes in English and Swedish translations

The present study is an explorative, corpus-based contrastive study of N-Rhemes in English and Swedish original texts, as well as translations between the two languages. The aim is twofold, to describe the N-Rheme in English and Swedish Fiction and Popular Science texts, and to examine translation correspondences, and lack of correspondences, between English and Swedish N-Rhemes. The first part of the investigation shows that N-Rhemes are very similar in the two languages and the two text types. The main differences are to a great extent related to word order differences between the two languages, e.g. the V2-constraint in Swedish and Subject prominence in English. However, word order is not the only explanation. Frequently, there is interplay between word order and information structure, as Swedish is more backwards-oriented and seems to follow the principle of end-weight more strictly than English. The analysis of the translation (non)-correspondences: Full Match, Reformulation, Movement and Restructuring shows that more translation changes occur in the translations into English. Reformulations are most frequent and typically result in unit shifts, function shifts and explicitness changes. Furthermore, the results show that English and Swedish clearly have different clause structure preferences. English favours hypotactic structures where Swedish has paratactic structures, which is reflected in the translations. In the translations into Swedish, clauses are frequently split, resulting in T-units that are informationally less dense, whereas in the translations into English, clauses are merged, resulting in informationally denser clauses. When information density is increased or decreased, this frequently results in explicitness changes. Finally, many of the translation changes could be seen as related to the character of the N-Rheme. N-Rhemes are often long and complex, and present newsworthy information. The longer the N-Rheme, the more information that potentially could be changed in the translation process. The great number of Reformulations and Restructurings reflects how translation changes occur with a purpose to ascertain that the goals of the texts are preserved, and even made clearer in the translation

Using Beatboxing for Creative Rehabilitation After Laryngectomy:Experiences From a Public Engagement Project

Laryngectomy is the surgical removal of the larynx (voice box), usually performed in patients with advanced stages of throat cancer. The psychosocial impact of losing the voice is significant, affecting a person’s professional and social life in a devastating way, and a proportion of this patient group subsequently must overcome depression (22–30%) and social isolation (40%). The profound changes to anatomical structures involved in voicing and articulation, as a result of surgery, radiotherapy or chemotherapy (separately or in combination with one another), introduce challenges faced in speech rehabilitation and voice production that complicate social reintegration and quality of life. After laryngectomy, breathing, voicing, articulation and tongue movement are major components in restoring communication. Regular exercise of the chest, neck and oropharyngeal muscles, in particular, is important in controlling these components and keeping the involved structures supple. It is, however, a difficult task for a speech therapist to keep the patient engaged and motivated to practice these exercises. We have adopted a multidisciplinary approach to explore the use of basic beatboxing techniques to create a wide variety of exercises that are seen as fun and interactive and that maximize the use of the structures important in alaryngeal phonation. We herein report on our empirical work in developing patients’ skills, particularly relating to voiced and unvoiced consonants to improve intelligibility. In collaboration with a professional beatboxing performer, we produced instructional online video materials to support patients working on their own and/or with support from speech therapists. Although the present paper is focused predominantly on introducing the structure of the conducted workshops, the rationale for their design and the final public engagement performance, we also include feedback from participants to commence the critical discourse about whether this type of activity could lead to systematic underlying research and robustly assessed interventions in the future. Based on this exploratory work, we conclude that the innovative approach that we employed was found to be engaging, useful, informative and motivating. We conclude by offering our views regarding the limitations of our work and the implications for future empirical research

Development and Sustainability of National Food Composition Databases for use in Dietary Monitoring and Public Health Nutrition in the Eastern Mediterranean Region

Background:Similar to Western Countries, the Eastern Mediterranean Region (EMR) also presents major public health issues associated with the increased consumption of sugar, fat (saturated fatty acids, trans fatty acids), salt. Therefore, one of the policies of the World Health Organization’s (WHO) EMRO is to reduce the intake of these, to address the risk of obesity and non-communicable diseases such as diabetes, cardiovascular disease and cancer. In order to do this, access to updated, standardized, harmonized food composition data (FCD) is essential. Aims: Objectives within this Medical Research Council GCRF project, working jointly with WHO–EMRO, are to assess the status of national FCD and to provide training and capacity development in the use of improved standardized methodologies to update FCD as well as dietary intake methods, use of suitable biomarkers of nutritional value and to determine health outcomes in the low- and middle-income countries (LMIC) of this region. By identifying specific regional needs for FCD compilation, detailed training workshops can be developed to enable the production of vital high-quality harmonised data in the EMR including: Iran, Iraq, Pakistan, Kuwait, Tunisia, Morocco, Sudan, Egypt, Jordan together with Mauritania. This capacity building will lead to the development and sustainability of up-to-date national and regional FCD for use in dietary monitoring assessment in food and nutrient intakes. Methods: Training needs were identified, and short-term scientific missions organized for researchers via training, knowledge exchange workshops and short-term exchange of researchers. Training at CAPNUTRA (Serbia) and INNTA (Tunisia) included the use of improved standardized methodologies for food composition and food intake for 7 EMR countries leading to development of national FCD, enabling upload onto the EuroFIR data platform. A 3-week training course on analytical methods was carried out at INSA (Portugal) for analysts from Egypt, Jordan and Sudan. Key findings: A total of 45 participants from 13 countries including 10 EMR and 3 invited West African countries attended 5 workshops and training exchanges. Training topics included: value documentation and quality assessment; food composition data tools (Food Composition And System Environment (FoodCASE), Diet assess and Plan (DAP), Nutritics; food classification and description of composite dishes, recipe calculation approaches; use of yield and retention factors; EuroFIR e-learning tools and case studies; laboratory food analysis (vitamins A, B1, B2, C, D2, D3 and E, fatty acids, amino acids, minerals, fibre); quality management system; food metrology principles; validation of chromatographic methods; and food label legislation. 6 countries have imported their FCD, as open access, into the EuroFIR FoodEXplorer platform. The WHO-EMRO jointly with MRC GCRF project funded and mobilized research institutions in over 10 countries, with more focus on identifying traditional dishes and micronutrients. Conclusions and project Implications: The use of improved standardized methodologies for food composition and dietary intake will produce robust measurements that will reinforce dietary monitoring and policy in LMIC. The capacity building from this project has led to searchable national food composition data from developing/emerging countries being made available in an open access form for the first time. WHO-EMRO, is funding further updates of FCD tables in Jordan, Lebanon, Oman, Sudan, Tunisia, Morocco, Pakistan, Iran Egypt, and UAE, with the focus on identifying TFA, SFA, salt and sugar in addition to micronutrients.Project supported by Global Challenges Research Funds (UK) and Medical Research Council (MR/R019576/1), is grateful to WHO EMRO.info:eu-repo/semantics/publishedVersio

Inertial Sensing to Determine Movement Disorder Motion Present before and after Treatment

There has been a lot of interest in recent years in using inertial sensors (accelerometers and gyroscopes) to monitor movement disorder motion and monitor the efficacy of treatment options. Two of the most prominent movement disorders, which are under evaluation in this research paper, are essential tremor (ET) and Parkinson’s disease (PD). These movement disorders are first evaluated to show that ET and PD motion often depict more (tremor) motion content in the 3–12 Hz frequency band of interest than control data and that such tremor motion can be characterized using inertial sensors. As well, coherence analysis is used to compare between pairs of many of the six degrees-of-freedom of motions under evaluation, to determine the similarity in tremor motion for the various degrees-of-freedom at different frequency bands of interest. It was quite surprising that this coherence analysis depicts that there is a statistically significant relationship using coherence analysis when differentiating between control and effectively medicated PD motion. The statistical analysis uncovers the novel finding that PD medication induced dyskinesia is depicted within coherence data from inertial signals. Dyskinesia is involuntary motion or the absence of intended motion, and it is a common side effect among medicated PD patients. The results show that inertial sensors can be used to differentiate between effectively medicated PD motion and control motion; such a differentiation can often be difficult to perform with the human eye because effectively medicated PD patients tend to not produce much tremor. As well, the finding that PD motion, when well medicated, does still differ significantly from control motion allows for researchers to quantify potential deficiencies in the use of medication. By using inertial sensors to spot such deficiencies, as outlined in this research paper, it is hoped that medications with even a larger degree of efficacy can be created in the future

Development and Sustainability of Eastern Mediterranean Region and South African National Food Composition Databases

Introduction: The World Health Organization’s (WHO)-Eastern Mediterranean Region Office (EMRO) aims to reduce the consumption of sugar, fat (saturated fatty acids, trans fatty acids) and salt; and decrease the risk of obesity and non-communicable diseases in the Eastern Mediterranean Region (EMR). To address this Quadram Institute Bioscience is working jointly with WHO-EMRO in providing training and capacity development to national experts, leading to standardized, harmonized, comprehensive, open access Food Composition Data (FCD) to underpin food and nutrition programs and policies in these low- and middle-income countries (LMIC). Materials and Methods: By identifying specific regional needs for FCD compilation, detailed training workshops were developed to enable the production of vital high-quality harmonised data in the EMR including: Iran, Iraq, Pakistan, Kuwait, Tunisia, Morocco, Sudan, Egypt, and Jordan. Training on standardized methodologies for food composition and dietary intake methods, biomarkers, analytical methods and FCD tools were provided by experts from UK, Serbia, Portugal and WHO-EMRO, via knowledge exchange workshops and short-term training exchange of researchers. Results: A total of 45 FCD expert compilers from 13 countries attended 2 workshops and 3 training exchanges. Knowledge transfer consisted of: value documentation; quality assessment; online food composition data tools; food classification and description of composite dishes; recipe calculation; yield and retention factors; and laboratory food analysis (vitamins A, B1, B2, C, D2, D3 and E, fatty acids, amino acids, minerals, fibre). FCD from 6 countries was standardized using the EuroFIR data template and Theasuri (standardised vocabularies). The final datasets from Iran, Iraq, Pakistan, Kuwait, Tunisia and Morocco were made available via FoodExplorer an innovative interface for FCD which allows users to search information from food composition data simultaneously across many countries. Discussion: The use of improved standardized methodologies for food composition and dietary intake will produce robust measurements that will reinforce dietary monitoring and policy in LMIC. The capacity building from this project has led to searchable national food composition data from LMIC being made available as open access form for the first time. WHO-EMRO, is funding further updates of FCD tables in Jordan, Lebanon, Oman, Sudan, Tunisia, Morocco, Pakistan, Iran, Egypt, and UAE, with the focus on identifying TFA, SFA, salt and sugar in addition to micronutrients.Project supported by Global Challenges Research Funds (UK) and Medical Research Council (MR/R019576/1), is grateful to WHO EMRO.info:eu-repo/semantics/publishedVersio

Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation

Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health

[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography

Purpose 111In (typically as [111In]oxinate3) is a gold standard radiolabel for cell tracking in humans by scintigraphy. A long half-life positron-emitting radiolabel to serve the same purpose using positron emission tomography (PET) has long been sought. We aimed to develop an 89Zr PET tracer for cell labelling and compare it with [111In]oxinate3 single photon emission computed tomography (SPECT). Methods [89Zr]Oxinate4 was synthesised and its uptake and efflux were measured in vitro in three cell lines and in human leukocytes. The in vivo biodistribution of eGFP-5T33 murine myeloma cells labelled using [89Zr]oxinate4 or [111In]oxinate3 was monitored for up to 14 days. 89Zr retention by living radiolabelled eGFP-positive cells in vivo was monitored by FACS sorting of liver, spleen and bone marrow cells followed by gamma counting. Results Zr labelling was effective in all cell types with yields comparable with 111In labelling. Retention of 89Zr in cells in vitro after 24 h was significantly better (range 71 to >90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with 111In or 89Zr (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for 111In. In liver, spleen and bone marrow at least 92 % of 89Zr remained associated with eGFP-positive cells after 7 days in vivo. Conclusion [89Zr]Oxinate4 offers a potential solution to the emerging need for a long half-life PET tracer for cell tracking in vivo and deserves further evaluation of its effects on survival and behaviour of different cell types